GENOTYPES FOR THE CYTOCHROME-P450 ENZYMES CYP2D6 AND CYP2C19 IN HUMANLONGEVITY - ROLE OF CYP2D6 AND CYP2C19 IN LONGEVITY

Objective: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute to longevity, we genotyped 241 Danish nonagenarians and cen tenarians for CYP2D6 and CYP2C19. Methods: For CYP2D6 we identified th e alleles CYP2D61, CYP2D6*3 and CYP2D6*4 with allele-specific polymer ase chain reaction (PCR). The CYP2D65 alleles were identified with a long PCR method. For CYP2C19 we identified the alleles CYP2C191, CYP2 C192 and CYP2C19*3 with an oligonucleotide ligation assay. Results: T he four alleles for CYP2D6 did not occur in Hardy-Weinberg proportions . The frequency of poor metabolism was slightly higher (10.2%) than ex pected [7.7%; odds ratio (OR) = 1.36 (0.75-2.40)]. The genotypes for C YP2C19 occur in Hardy-Weinberg proportions. The frequency of poor meta bolism (3.8%) was not significantly different from a young control gro up [3.1%; OR = 1.21 (0.26-5.75)]. Conclusion: CYP2D6 could play a role in human longevity due to the lack of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by protecting the poor metaboliz ers from cancer, we should expect a rise in the frequency in these gen otypes in Denmark from 7.7% among young adults to 10-11% among very ol d people. We found a frequency of poor metabolism of 10.2% in the very old group. CYP2C19 is - due to the occurrence of Hardy-Weinberg propo rtions and the expected number of poor metabolizers - unlikely to cont ribute to human longevity.